Investigating the neural and behavioral correlates of the stress-rumination link in healthy humans by modulating the left Dorsolateral Prefrontal Cortex using Theta Burst Stimulation

Figures

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  Fig. 1. The allocation of experimental groups (A) and overview of the experimental procedure (B). Above the line, the respective tasks and experimental phases are shown. Below the line, the time points of questionnaire assessments are displayed in bold, with the names of the corresponding questionnaires highlighted in blue. RRS = Ruminative Response Scale; TBS = Theta Burst Stimulation; BDI-II = Beck's Depression Inventory II; PANAS = Positive and Negative Affect Schedule; SRSRQ = Stress-Reactive State Rumination Questionnaire; stress = subjective stress assessed via a Visual Analogue Scale (0–100%); *Only assessed at the first appointment (AP1)

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  Fig. 2. Line plot of the contrasts of subjective stress ratings dependent on order of conditions (A = sham stimulation at the first appointment, active stimulation at the second appointment; B = active stimulation at the first appointment, sham stimulation at the second appointment), and line plot of raw data of subjective stress ratings dependent on the appointment (C = first appointment; D = second appointment). rest = resting-state measurement; ctl1 = control task 1; ctl2 = control task 2; TSST = Trier Social Stress Test; sTBS = sham Theta Burst Stimulation; cTBS = continuous Theta Burst Stimulation; iTBS = intermittent Theta Burst Stimulation; 15 min = 15 min after the TSST; RRS = Ruminative Response Scale. Please note that the effect of the order of stimulation conditions is visually depicted within the plots of the different appointments (first appointment: sTBS = participants with order of stimulation conditions sham → active; iTBS and cTBS = participants with order of stimulation conditions active → sham; second appointment: vice versa). Error bars indicate 1 standard error of the mean

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  Fig. 3. Line plot of the contrasts of state rumination ratings dependent on order of conditions (A = sham stimulation at the first appointment, active stimulation at the second appointment; B = active stimulation at the first appointment, sham stimulation at the second appointment), and line plot of raw data of state rumination ratings dependent on order of conditions and appointment (C = first appointment sham stimulation; D = first appointment active stimulation; E = second appointment active stimulation; F = second appointment sham stimulation). rest = resting-state measurement; 60 min post TSST = 60 min after the Trier Social Stress Test; RRS = Ruminative Response Scale. Error bars indicate 1 standard error of the mean

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  Fig. 4. Line plot of the contrasts of negative affect ratings dependent on order of conditions (A = sham stimulation at the first appointment, active stimulation at the second appointment; B = active stimulation at the first appointment, sham stimulation at the second appointment) and line plot of raw data of negative affect ratings dependent on the appointment (C = first appointment; D = second appointment). rest = resting-state measurement; sTBS = sham Theta Burst Stimulation; cTBS = continuous Theta Burst Stimulation; iTBS = intermittent Theta Burst Stimulation; 0 min post TSST = 0 min after the Trier Social Stress Test; RRS = Ruminative Response Scale. Please note that the effect of the order of stimulation conditions is visually depicted within the plots of the different appointments (first appointment: sTBS = participants with order of stimulation conditions sham → active; iTBS and cTBS = participants with order of stimulation conditions active → sham; second appointment: vice versa). Error bars indicate 1 standard error of the mean

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  Fig. 5. Plots of the t-values of the paired t-tests in each channel testing the active stimulation condition against the sham stimulation in each channel dependent on the stimulation condition A = cTBS, B = iTBS, TSST = arithmetic task of the TSST. The figure legend was scaled so that channels showing a significant t-value are displayed in blue (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\le$$\end{document}≤−1.66) or red (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}≥ 1.66). Significant channels in the cTBS condition are channel 9 (left VLPFC), 22, 34, 36 (SAC), 41, and 42. Significant channels in the iTBS condition are channel 7 (left VLPFC), 33, and 34

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  Fig. 6. The z-standardized hemodynamic responses during the arithmetic task of the TSST in the left DLPFC in low and high ruminators depending on the TBS-condition at the first appointment (A) and the second appointment (B). A.1, A.2, B.1, and B.2 illustrate the raw data. A.3, A.4, B.3, and B.4 illustrate the contrasts (cTBS minus sTBS and iTBS minus sTBS). The light shading marks the 40 s trial and the dark shading the 20 s pause to allow the hemodynamic response to recover. Shadings around the hemodynamic curves reflect standard errors of the mean. The baseline includes the 5 s before each trial; 0 s on the x-axis marks the beginning of the trial. See supplementary material S11 for the time series of the other ROIs